Non-insulin dependent diabetes mellitus (NIDDM) is a common, chronic disease with increasing incidence in the United States, responsible for an enormous burden of morbidity and mortality. Most of the morbidity, mortality, and financial burden of NIDDM is related to the development of complications. Consequently, prevention of NIDDM, or even a substantial delay in disease onset, will have a major financial and health impact in this country. Compelling evidence exists to indicate that insulin resistance is an early defect present in the pre-diabetic state. Consequently, it is logical to direct primary prevention interventions at improving this metabolic defect. It is well established that physical exercise is a lifestyle intervention which can ameliorate insulin resistance, and therefore, might prevent NIDDM. Troglitazone is a newly avail-able oral hypoglycemic agent, from the Thiozoladinedione class of drugs. This agent exerts its effects primarily by improving insulin resistance, and this has been demonstrated in NIDDM and IGT populations. Consequently, we propose a 2 X 2 factorial design in which patients will be randomly assigned in a double blind fashion to either Troglitazone, placebo, exercise, or Troglitazone plus exercise groups. The study will be performed in patients with IGT, as well as in those with NIDDM who do not have fasting hyperglycemia. Power calculations indicate that a total of 4,000 patients in this multi-center cooperative trial will be sufficient to detect positive outcomes, and this will incorporate approximately 200 patients/Clinical Center. This study cohort will consist of patients with IGT, former gestational diabetes mellitus, NIDDM without fasting hyperglycemia, and approximately 50% of all subjects should be from minority populations. This study will be conducted over 7 years, including a planning phase, recruitment phase, 4-5 year treatment phase, and close out phase. This study should provide a rigorous test of the hypothesis that the proposed interventions will prevent NIDDM.